Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
Res Sq ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38746209

ABSTRACT

Our study focuses on the intricate connection between tissue-level organization and ciliated organ function in humans, particularly in understanding the morphological organization of airways and their role in mucociliary clearance. Mucociliary clearance is a key mechanical defense mechanism of human airways, and clearance failure is associated with many respiratory diseases, including chronic obstructive pulmonary disease (COPD) and asthma. While single-cell transcriptomics have unveiled the cellular complexity of the human airway epithelium, our understanding of the mechanics that link epithelial structure to clearance function mainly stem from animal models. This reliance on animal data limits crucial insights into human airway barrier function and hampers the human-relevant in vitro modeling of airway diseases. This study, for the first time, maps the distribution of ciliated and secretory cell types along the airway tree in both rats and humans, noting species-specific differences in ciliary function and elucidates structural parameters of airway epithelia that predict clearance function in both native and in vitro tissues alike. By uncovering how tissue organization influences ciliary function, we can better understand disruptions in mucociliary clearance, which could have implications for various ciliated organs beyond the airways.

2.
bioRxiv ; 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38187619

ABSTRACT

Mucociliary clearance is a key mechanical defense mechanism of human airways, and clearance failure is linked to major respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. While single-cell transcriptomics have unveiled the cellular complexity of the human airway epithelium, our understanding of the mechanics that link epithelial structure to clearance function mainly stem from animal models. This reliance on animal data limits crucial insights into human airway barrier function and hampers the human-relevant in vitro modeling of airway diseases. Our study fills this crucial knowledge gap and for the first time (1) maps the distribution of ciliated and secretory cell types on the mucosal surface along the proximo-distal axis of the rat and human airway tree, (2) identifies species-specific differences in ciliary beat and clearance function, and (3) elucidates structural parameters of airway epithelia that predict clearance function in both native and in vitro tissues alike. Our broad range of experimental approaches and physics-based modeling translate into generalizable parameters to quantitatively benchmark the human-relevancy of mucociliary clearance in experimental models, and to characterize distinct disease states.

3.
Cells ; 12(11)2023 05 24.
Article in English | MEDLINE | ID: mdl-37296588

ABSTRACT

Primary ciliary dyskinesia (PCD) is a rare heterogenic genetic disorder associated with perturbed biogenesis or function of motile cilia. Motile cilia dysfunction results in diminished mucociliary clearance (MCC) of pathogens in the respiratory tract and chronic airway inflammation and infections successively causing progressive lung damage. Current approaches to treat PCD are symptomatic, only, indicating an urgent need for curative therapeutic options. Here, we developed an in vitro model for PCD based on human induced pluripotent stem cell (hiPSC)-derived airway epithelium in Air-Liquid-Interface cultures. Applying transmission electron microscopy, immunofluorescence staining, ciliary beat frequency, and mucociliary transport measurements, we could demonstrate that ciliated respiratory epithelia cells derived from two PCD patient-specific hiPSC lines carrying mutations in DNAH5 and NME5, respectively, recapitulate the respective diseased phenotype on a molecular, structural and functional level.


Subject(s)
Ciliary Motility Disorders , Induced Pluripotent Stem Cells , Humans , Respiratory System , Epithelium , Ciliary Motility Disorders/genetics , Phenotype , NM23 Nucleoside Diphosphate Kinases
SELECTION OF CITATIONS
SEARCH DETAIL
...